The work proposed in this research proposal concerns an X-ray crystallographic determination of a large number of purine-pyrimidine monomeric crystalline complexes in an effort to understand the precise nature of their hydrogen-bonding specificity. In addition, the method of co-crystallization has been extended to include the interaction between drugs and nucleic acids, and during the tenure of the award we have established the manner of actinomycin-DNA binding through an X-ray analysis of an actinomycin-deoxyguanosine crystalline complex. We are continuing our efforts to provide further information in this area of drug-nucleic acid complex formation.